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Cabergoline
Updated 2010 Dec 08 09:33:00 AM: adjuvant therapy in later disease may reduce off-time and levodopa use and improve Unified Parkinson's Disease Rating Scale scores in patients with motor complications (Cochrane Database Syst Rev 2010 Jul 7) update
AHFS data updated
addition of prolonged-release ropinirole to levodopa therapy may delay onset of dyskinesia in patients with Parkinson disease (Mov Disord 2010 May 15) update
Related Summaries:
Hyperprolactinemia
Parkinson disease
Overview:
ergot-derivative dopamine receptor agonist and prolactin inhibitor
brand name Dostinex, available generically
FDA approved for treatment of hyperprolactinemia
initial dose 0.25 mg orally twice weekly
increase by 0.25 mg twice weekly up to 1 mg twice weekly, use lowest effective dose
consider decreasing dose if normal serum prolactin levels for 24 months and tumor size decreased ≥ 50%
cabergoline appears at least as effective and better tolerated than bromocriptine in women with hyperprolactinemia (level 2 [mid-level] evidence)
has been used for Parkinson disease but other dopamine agonists more commonly used
contraindicated if uncontrolled hypertension
adverse effects may include pleural effusion, pulmonary fibrosis, cardiac valvulopathy, orthostatic hypotension, nausea, constipation, abdominal pain, headache, dizziness, asthenia, fatigue
cabergoline may be associated with cardiac valve regurgitation (level 2 [mid-level] evidence)
Pregnancy Category B
available in 0.5 mg scored tablets
General Information
Description:
An ergot-derivative dopamine receptor agonist and prolactin inhibitor. 1 2 3 8 10 11 12 15
Class:
Class: Ergot-derivative Dopamine Receptor Agonists
Brand:
Dostinex®
Chemical Name:
1-[(6-allylergolin-8β-yl)-carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea
Uses and Efficacy
Uses:
Hyperprolactinemic Disorders:
Treatment of hyperprolactinemic disorders due to prolactinoma (prolactin-secreting adenomas) or idiopathic hyperprolactinemia. 1 2 3 12 13 14 Suppresses prolactin secretion, restores gonadal function, and reduces the size of prolactinomas. 1 2 3 12 13 14
At least as effective as bromocriptine in normalizing serum prolactin concentrations and restoring gonadal function in women with hyperprolactinemic amenorrhea. 12 13 Fewer adverse effects, especially adverse GI effects, reported in cabergoline-treated women than in bromocriptine-treated women. 12 13 14 Bromocriptine preferred when restoration of fertility is the goal of therapy; this recommendation is based on the safety record of bromocriptine in pregnant women. 14
Parkinsonian Syndrome:
Has been used for the symptomatic management of parkinsonian syndrome †. 4 5 6 7 8 9 10 11
Has been used as monotherapy for initial symptomatic management of parkinsonian syndrome †. 8 9 11 Most clinicians would use levodopa for initial therapy in individuals >70 years of age (less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction), in patients with cognitive impairment, and in those with severe disease. 7 A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age. 7
Has been used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome † in patients with advanced disease. 4 5 6 8 10
Efficacy:
Hyperprolactinemia:
cabergoline appears at least as effective and better tolerated than bromocriptine in women with hyperprolactinemia (level 2 [mid-level] evidence)
based on randomized trial with partial blinding
459 amenorrheic women with pituitary microadenomas or idiopathic hyperprolactinemia were randomized to cabergoline 0.5-1 mg twice weekly vs. bromocriptine 2.5-5 mg twice daily
treatment was double-blind for 8 weeks then open-label to allow unbiased assessment of side effects initially
comparing cabergoline vs. bromocriptine
stable normoprolactinemia in 83% vs. 59% (p < 0.001, NNT 5)
ovulatory cycles or pregnancy occurred in 72% vs. 52% (p < 0.001, NNT 5)
amenorrhea persisted in 7% vs. 16%
adverse effects in 68% vs. 78% (p = 0.03, NNT 10), or 63% vs. 71% during double-blind period (p = 0.07)
drug discontinuation due to adverse effects in 3% vs. 12% (p < 0.001, NNT 12)
nausea in 31% vs. 50% (p < 0.001, NNT 6)
Reference - N Engl J Med 1994 Oct 6;331(14):904
Parkinson disease:
cabergoline can reduce levodopa dose and may modestly improve motor impairment and disability
based on Cochrane review
systematic review of 3 trials with 268 patients with Parkinson disease and motor complications
reduction of 1.14 hours (95% CI -0.06 to 2.33, p = 0.06) in off time in favor of cabergoline was not statistically significant
inadequate data on dyskinesia
levodopa dose reduction was significantly greater with cabergoline
nonsignificant trend towards more dopaminergic adverse events with cabergoline
nonsignificant trend towards fewer withdrawals from cabergoline
Reference - systematic review last updated 2000 Nov 17 (Cochrane Library 2001 Issue 1:CD001518)
cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment, disability ratings, and levodopa dose reduction over the first 3 months of therapy
based on Cochrane review
systematic review of 5 trials with 1,071 patients
adverse event profile and withdrawals similar except dyskinesia and confusion were increased with cabergoline
Reference - systematic review last updated 2000 Nov 17 (Cochrane Library 2001 Issue 1:CD001519)
dopamine agonists for Parkinson disease (drug class considerations)
dopamine agonist may reduce risk of motor complications but associated with more adverse events than levodopa in patients with early Parkinson disease (level 2 [mid-level] evidence)
based on Cochrane review of trials with methodologic limitations
systematic review of 29 randomized trials evaluating oral dopamine agonist therapy in 5,247 patients with early Parkinson disease
methodologic limitations included inadequate or unclear description of randomization (16 trials) and allocation concealment (23 trials), unclear use of intention-to-treat analysis
compared to levodopa alone, dopamine agonist (with or without levodopa) associated with reduced incidence of
dyskinesia in 18 trials with 3,404 patients (p < 0.00001), results limited by heterogeneity (p = 0.006)
dystonia in 11 trials with 1,896 patients (p = 0.0002)
motor fluctuations in 12 trials with 2,580 patients (p = 0.002)
comparing dopamine agonists (with or without levodopa) to control (placebo or levodopa) on adverse effects
dopamine agonists associated with increased
edema in analysis of 6 trials with 1,650 patients
odds ratio 3.48 (95% CI 2.53-4.79)
NNH 6-14 assuming 5% edema in controls
somnolence in analysis of 11 trials with 2,423 patients
odds ratio 2.18 (95% CI 1.75-2.72)
NNH 7-14 assuming 11% somnolence in controls
constipation in analysis of 8 trials with 1,961 patients
odds ratio 1.8 (95% CI 1.36-2.39)
NNH 9-35 assuming 9% constipation in controls
dizziness in analysis of 13 trials with 2,294 patients
odds ratio 1.6 (95% CI 1.28-2.01)
NNH 8-29 assuming 15% dizziness in controls
hallucinations in analysis of 14 trials with 2,479 patients
odds ratio 2.22 (95% CI 1.58-3.12)
NNH 13-45 assuming 4% hallucinations in controls
nausea in 34.4% vs. 23.1% in analysis of 15 trials with 2,631 patients
odds ratio 1.86 (95% CI 1.56-2.23)
NNH 5-11 assuming 23% nausea in controls
discontinuation of treatment due to adverse events in 16.3% vs. 7% in analysis of 25 trials with 4,719 patients
odds ratio 2.49 (95% CI 2.08-2.98)
NNH 8-15 assuming 7% discontinuation of treatment in controls
symptomatic control of Parkinson disease better with levodopa than dopamine agonists, but data too inconsistent and incomplete for meta-analysis
Reference - Cochrane Database Syst Rev 2008 Apr 16;(2):CD006564, Cochrane for Clinicians summary can be found in Am Fam Physician 2009 Jul 1;80(1):28
addition of dopamine agonists to levodopa therapy may improve activities of daily function but increase rates of dyskinesia and hallucinations in patients with Parkinson disease (level 2 [mid-level] evidence)
based on systematic review without assessment of allocation concealment
systematic review of 15 randomized placebo-controlled trials of dopamine agonist in 4,380 patients with Parkinson disease on levodopa therapy
non-ergot dopamine agonists (pramipexole, ropinirole, sumanirole, piribedil and rotigotine) and ergot dopamine agonists (pergolide, cabergoline and bromocriptine) were evaluated; treatments lasted 12-40 weeks
trial quality assessment did not evaluate allocation concealment or intention-to-treat analysis
use of adjunct dopamine agonist associated with
improved activities of daily living scores (p < 0.0001) in analysis of 10 trials with 2,335 patients
improved motor scores (p < 0.0001) in analysis of 9 trials with 2,226 patients, analysis limited by statistical heterogeneity
reduction in "off" time (p < 0.0001) in analysis of 4 trials with 1,851 patients, analysis limited by statistical heterogeneity
reduction in levodopa dose (p < 0.0001) in analysis of 5 trials with 1,233 patients
increased rate of dyskinesias in analysis of 12 trials with 4,076 patients
odds ratio 3.34 (95% CI 2.71-4.11)
NNH 4-6 assuming 12% dyskinesias in controls
increased rate of hallucinations in analysis of 13 trials with 4,082 patients
odds ratio 3.58 (95% CI 2.64-4.86)
NNH 9-21 assuming 3% hallucinations in controls
no significant difference between dopamine agonist and placebo groups in number of patient withdrawals
Reference - Int J Clin Pract 2009 Apr;63(4):613
adjuvant therapy in later disease may reduce off-time and levodopa use and improve Unified Parkinson's Disease Rating Scale scores in patients with motor complications (level 2 [mid-level] evidence)
based on Cochrane review with inadequate assessment of trial quality
systematic review of 44 randomized placebo-controlled trials evaluating oral dopamine agonists, COMT inhibitors, or MAO-B inhibitors as adjuvant therapy to levodopa in 8,436 patients with later stage Parkinson disease experiencing motor complication
quality assessment included only randomization sequence generation (adequate in 26 trials), allocation concealment (adequate in 5 trials), and blinding (adequate in all trials)
indirect comparisons suggest dopamine agonists more effective than COMT inhibitors and MAO-B inhibitors
Reference - Cochrane Database Syst Rev 2010 Jul 7;(7):CD007166
Restless legs syndrome:
cabergoline is effective for restless leg syndrome (level 1 [likely reliable] evidence)
based on randomized trial
40 patients ages 18-75 years with restless leg syndrome were randomized to cabergoline vs. placebo at bedtime for 5 weeks
cabergoline 0.5 mg dose was increased in 0.5 mg increments over 14 days to final dose of 2 mg
domperidone could be prescribed for any patients complaining of gastrointestinal side effects
comparing cabergoline vs. placebo
mean periodic leg movements during sleep arousal index < 5/hour vs. 20/hour (p = 0.0014)
mean improvement of 23.7 vs. 11.4 on 60-point scale measuring quality of life (p < 0.05)
80% vs. 30% were very much or much improved on Clinical Global Impressions Scale (p < 0.01, NNT 2)
65% vs. 30% adverse effects (NNH 3)
22% vs. 5% nausea (NNH 5)
9% vs. 0 constipation (NNH 11)
13% vs. 0 discontinuation due to adverse effects (NNH 7)
Reference - Neurology 2006 Sep 26;67(6):1040
Dosage and Administration
Administration:
Oral Administration:
Administer orally without regard to meals. 1
Hyperprolactinemic disorders: Administer twice weekly. 1
Parkinsonian syndrome: Administer once daily. 8
Dosage:
Adults:
Hyperprolactinemic Disorders:
Oral:
Initiate at low dosage and increase slowly (at ≥4 week intervals) until therapeutic response is achieved. 1
Initially, 0.25 mg twice weekly; increase in increments of 0.25 mg twice weekly up to 1 mg twice weekly. 1 Base dosage adjustments on serum prolactin concentrations; use lowest effective dosage. 1
Consider decreasing the dosage if normal serum prolactin concentrations maintained for 24 months and size of tumor decreased ≥50%; periodically monitor to determine whether retreatment is needed. 14 15 Some patients (e.g., those with microadenomas) may be able to discontinue the drug; discontinuance in those with macroadenomas should be undertaken with extreme caution. 14 15 The manufacturer states that efficacy >24 months not established. 1
Parkinsonian Syndrome †:
Oral:
Initiate at low dosage and increase slowly (at intervals of 7 or 14 days) until the maximum therapeutic response is achieved. 8
2–6 mg daily has been used. 8
Therapy has been initiated with 1 mg once daily, then increased in increments of 0.5–1 mg at 7 or 14 day intervals until control of symptoms obtained. 8
When cabergoline is used as an adjunct to levodopa, the levodopa dosage may be decreased gradually as tolerated. 8
When therapy with a dopamine receptor agonist is discontinued, the drug is discontinued gradually. 18
Prescribing Limits:
Adults:
Hyperprolactinemic Disorders:
Oral:
Dosages >1 mg twice weekly have not been systematically evaluated. 1
Special Populations:
Hepatic Impairment:
No specific dosage recommendations at this time; use with caution in patients with severe hepatic impairment. 1 (See Hepatic Impairment under Cautions and also see Absorption: Special Populations, under Pharmacokinetics.)
Renal Impairment:
No specific dosage recommendations at this time. 1(See Elimination: Special Populations, under Pharmacokinetics.)
Geriatric Patients:
Select dosage carefully; start at low dosage. 1(See Geriatric Use under Cautions.)
Cautions and Adverse Effects
Contraindications:
Known hypersensitivity to cabergoline or other ergot derivatives. 1
Uncontrolled hypertension. 1
Warnings/Precautions:
Warnings:
Hypertension during Pregnancy:
Should not be used in patients with pregnancy-induced hypertension (e.g., preeclampsia, eclampsia) unless potential benefits outweigh possible risks. 1
Fibrotic Effects:
Pleural effusion, pulmonary fibrosis, and cardiac valvulopathy reported. 1 16Signs and symptoms have improved after discontinuance. 1
Use with caution in patients with history of, or current signs and/or symptoms of, respiratory or cardiac disorders linked to fibrotic tissue. 1
General Precautions:
When used for parkinsonian syndrome, observe the usual precautions associated with dopamine receptor agonist therapy in this patient population. 8 9 17 18 Usual dosage for parkinsonian syndrome exceeds dosage used for hyperprolactinemia. 1 17
Symptomatic Hypotension:
Orthostatic hypotension reported, especially if initial doses >1 mg are used. 1 Exercise care in patients currently receiving drugs known to lower BP. 1
Postpartum Breast Engorgement:
Not indicated for the inhibition or suppression of lactation. 1 Hypertension, cerebrovascular accidents, and seizures reported rarely when another dopamine receptor agonist (i.e., bromocriptine) was used for this indication. 1
Specific Populations:
Pregnancy:
Category B. 1 (See Hypertension during Pregnancy under Cautions.)
Lactation:
Not known whether cabergoline is distributed into milk; drug is expected to interfere with lactation. 1 Discontinue nursing or the drug. 1
Pediatric Use:
Safety and efficacy not established. 1
Geriatric Use:
Insufficient experience from clinical studies to determine whether patients ≥65 years of age respond differently than younger adults. 1 Other clinical experience has not identified age-related differences in responses. 1
Select dosage carefully, generally initiating therapy at low dosage. 1 Consider the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or drug therapy in geriatric patients. 1 2 3
Hepatic Impairment:
Cabergoline extensively metabolized in liver; use with caution and monitor carefully. 1(See Absorption: Special Populations, under Pharmacokinetics.)
Common Adverse Effects:
Patients with hyperprolactinemia: Nausea, constipation, abdominal pain, headache, dizziness, asthenia, fatigue, somnolence. 1
Patients with parkinsonian syndrome †: Dyskinesia, hallucinations, confusion, peripheral edema. 1
Heart valvulopathy with dopamine agonists:
some dopamine agonists (pergolide or cabergoline) may be associated with cardiac valve regurgitation (level 2 [mid-level] evidence)
based on case-control study, and cohort studies with asymptomatic cases
nested case-control study
conducted within cohort of 11,417 patients ages 40-80 years in United Kingdom General Practice Research Database who were prescribed antiparkinsonian drugs (levodopa, selegiline, bromocriptine, cabergoline, pergolide, lisuride, pramipexole, ropinirole) 1988-2005
31 cases had newly diagnosed mitral regurgitation (26 cases), aortic regurgitation (12 cases) or tricuspid regurgitation (3 cases); 8 cases had multiple valves involved
663 controls matched on age, sex and year of entry
drugs associated with cardiac valve regurgitation were
pergolide (incidence rate ratio 7.1, 95% CI 2.3-22.3) based on 6 cases (19% cases vs. 4% controls)
cabergoline (incidence rate ratio 4.9, 95% CI 1.5-15.6) based on 6 cases (19% cases vs. 5% controls)
no cases had exposure to bromocriptine, lisuride, pramipexole or ropinirole and few (0 to 3%) controls had exposure to these drugs
Reference - N Engl J Med 2007 Jan 4;356(1):29, editorial can be found in N Engl J Med 2007 Jan 4;356(1):6, commentary can be found in N Engl J Med 2007 Apr 19;356(16):1676, ACP J Club 2007 May-Jun;146(3):75 EBSCOhost Full Text
pergolide use in Parkinson disease associated with heart valve disease (level 3 [lacking direct] evidence)
based on meta-analysis of 7 studies with 394 patients treated with pergolide mesylate and 280 controls (without clinical outcomes)
pergolide associated with moderate to severe regurgitation (odds ratio 3.1, 95% CI 1.7-5.6)
Reference - Arch Neurol 2007 Dec;64(12):1721
cohort studies using echocardiography
cabergoline and pergolide associated with moderate-to-severe cardiac valve regurgitation
echocardiography performed in
64 patients with Parkinson's disease taking pergolide for at least 12 months
49 patients with Parkinson's disease taking cabergoline for at least 12 months
42 patients with Parkinson's disease taking non-ergot-derived dopamine agonist (pramipexole or ropinirole) for at least 12 months
90 controls recruited from relatives of patients or acquaintances of medical staff
moderate-to-severe mitral regurgitation found in 9 (14%) pergolide group, 5 (10%) cabergoline group, 0 non-ergot-derived dopamine agonist group and 2 (2%) controls
moderate-to-severe aortic regurgitation found in 9 (14%) pergolide group, 12 (24%) cabergoline group, 0 non-ergot-derived dopamine agonist group and 3 (3%) controls
moderate-to-severe tricuspid regurgitation found in 4 (6%) pergolide group, 3 (6%) cabergoline group, 0 non-ergot-derived dopamine agonist group and 1 (1%) control
rate of any moderate-to-severe cardiac valve regurgitation
0 for patients exposed to non-ergot-derived dopamine agonists
6% for controls
23% for pergolide (NNH 5)
29% for cabergoline (NNH 4)
Reference - N Engl J Med 2007 Jan 4;356(1):39, editorial can be found in N Engl J Med 2007 Jan 4;356(1):6, commentary can be found in ACP J Club 2007 May-Jun;146(3):75 EBSCOhost Full Text
pergolide associated with restrictive valvular heart disease on echocardiography
78 Parkinson disease patients using pergolide and 18 Parkinson disease patients not taking pergolide underwent echocardiography
comparing pergolide users vs. controls
33% vs. 0 had restrictive valvular heart disease of any type
19% vs. 0 had "important" disease
Reference - Lancet 2004 Apr 10;363(9416):1179 EBSCOhost Full Text, commentary can be found in Lancet 2004 Jun 5;363(9424):1907 EBSCOhost Full Text, Am Fam Physician 2005 Feb 1;71(3):584
pergolide use may be associated with aortic regurgitation but not severe regurgitation
retrospective study of 118 patients who had "pergolide" or "Permax" in the typed medical record notes and had echocardiography
comparing 55 patients who had echocardiography at least 6 months after starting pergolide vs. 63 patients who had echocardiography before starting pergolide or within 1 month of starting pergolide
25 of 55 (45%) vs. 13 of 63 (21%) had aortic valve regurgitation (p = 0.006, NNH 4)
no significant differences in rates of tricuspid valve regurgitation (78% vs. 76%), mitral valve regurgitation (71% vs. 65%), any valve regurgitation (85% vs. 79%), severe tricuspid regurgitation (11% vs. 8%), severe mitral regurgitation (13% vs. 5%), severe aortic regurgitation (13% vs. 8%) or any severe regurgitation (24% vs. 14%)
Reference - Mayo Clin Proc 2005 Aug;80(8):1016 EBSCOhost Full Text
pergolide (Permax) associated with valvular heart disease in 15 reports collected by FDA (Mayo Clin Proc 2003 Jun;78(6):730 EBSCOhost Full Text PDF), editorial can be found in Mayo Clin Proc 2003 Jun;78(6):684 EBSCOhost Full Text PDF
case report of cabergoline-related severe restrictive mitral regurgitation can be found in N Engl J Med 2005 Nov 3;353(18):1976, commentary can be found in N Engl J Med 2006 Jan 26;354(4):420
Additional Adverse Effect Information:
dopamine agonists may increase risk of sudden uncontrollable somnolence (level 2 [mid-level] evidence)
based on observational studies
interview and medical record review of 929 Parkinson disease patients
22% reported sudden uncontrollable somnolence in preceding 6 months
episodes reported by 13% those taking levodopa-carbidopa monotherapy, 22% taking dopamine agonist monotherapy, and 28% taking both
Reference - Arch Neurol 2005 Aug;62(8):1242 in J Watch Online 2005 Aug 30
excessive daytime sleepiness reported in 51% of cohort of 638 highly functional Parkinson disease patients
16 patients (3.8%) had sudden onset of sleep while driving
daytime sleepiness and sleep attacks while driving were NOT associated with any antiparkinson drugs or drug classes
Reference - JAMA 2002 Jan 23-30;287(4):455, editorial can be found in JAMA 2002 Jan 23-30;287(4):509, commentary can be found in JAMA 2002 Apr 24;287(16):2076
review of sleep attacks with dopamine agonists identified 124 patients in 20 publications but found insufficient data to provide specific recommendations (BMJ 2002 Jun 22;324(7352):1483 full-text), commentary can be found in BMJ 2002 Sep 21;325(7365):657 full-text
initiation of dopamine agonist therapy may be associated with acute orthostatic hypotension (level 2 [mid-level] evidence)
based on study of 29 patients with Parkinson disease given pergolide, pramipexole or ropinirole then blood pressure measured supine and standing on 3 occasions
10 (34%) had orthostatic hypotension defined as drop in systolic blood pressure > 25 mm Hg or diastolic blood pressure > 10 mm Hg
only 3 (10%) had symptoms of orthostatic hypotension such as lightheadedness or malaise
Reference - Arch Neurol 2000 Oct;57(10):1461
pathological gambling reported in 11 patients within 30 months of starting dopamine agonist for Parkinson disease (level 3 [lacking direct] evidence)
effect within 3 months in 7 of these patients
17 other cases reported in the literature
19 of these 28 cases (68%) associated with pramipexole
Reference - Arch Neurol 2005 Sep;62(9):1377
new onset gambling or hypersexuality seen in 7 of 38 patients taking therapeutic doses of dopamine agonists or levodopa-carbidopa in retrospective study (Mayo Clin Proc 2009 Apr;84(4):310 EBSCOhost Full Text)
Interactions
Specific Drugs:
Drug Interaction Comments
Dopamine antagonists (e.g., phenothiazines, butyrophenones, thioxanthenes, metoclopramide) Possible reduced efficacy of cabergoline 1 Generally should not be used concomitantly 1 8
Levodopa Additive therapeutic and/or adverse (e.g., dyskinesia) effects 8 Consider a reduction in levodopa dosage when cabergoline is added to levodopa therapy 8
Mechanism of Action/Pharmacokinetics
Actions:
A long-acting dopamine receptor agonist; has high binding affinity for dopamine D2 receptors and lesser affinity for D1, α1- and α2-adrenergic, and serotonin (5-HT1 and 5-HT2) receptors. 1 8
Reduces serum prolactin concentrations by inhibiting release of prolactin from the anterior pituitary gland. 1 This effect on hypothalamic/pituitary function attributed to the drug's agonist activity at D2 receptors. 1
Pharmacokinetics:
Absorption:
Bioavailability:
Peak plasma concentrations usually attained within 1–2 hours. 1 17
Absolute bioavailability unknown. 1 17
Onset:
Following oral administration of a single 0.6-mg dose of cabergoline, time to maximum prolactin-lowering effect was 48 hours. 1
Duration:
Prolactin-lowering effect persists for 14 days. 1
Food:
Food does not alter the pharmacokinetics of cabergoline. 1
Special Populations:
Peak plasma concentrations and AUC not altered in patients with mild to moderate hepatic impairment (Child Pugh score ≤10). 1 Peak plasma concentrations and AUC substantially increased in patients with severe impairment (Child Pugh score >10). 1
Distribution:
Extent:
Extensively distributed throughout the body, including the CNS. 1 8
Plasma Protein Binding:
40–42%. 1 17
Elimination:
Metabolism:
Metabolized in the liver (minimal CYP involvement), mainly by hydrolysis of the acylurea bond; 1 17 undergoes substantial first-pass metabolism. 1
Elimination Route:
Excreted in feces (72%) and in urine (18% as metabolites and unchanged drug). 17
Half-life:
63–109 hours. 1 17
Special Populations:
Pharmacokinetic values not altered in patients with moderate to severe renal impairment. 1 17
Stability and Compatibility
Storage:
Oral:
Tablets:
20–25°C. 1
Preparations
Tables of Preparations:
Cabergoline Routes Dosage Forms Strengths Brand Names Manufacturer
Oral Tablets 0.5 mg Dostinex® (scored) Pfizer
Cabergoline Teva, Par
Medication Cost Assistance Programs:
medication cost assistance programs for Cabergoline from NeedyMeds
Patient Information
Advice to Patients:
Potential for hypotension. 1
Importance of patients informing clinicians if cough or dyspnea develop. 1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., respiratory or cardiac disorders associated with fibrosis). 1
Importance of informing patients of other important precautionary information. 1 (See Cautions.)
References
Updated 2010 Dec 08 09:33:00 AM: adjuvant therapy in later disease may reduce off-time and levodopa use and improve Unified Parkinson's Disease Rating Scale scores in patients with motor complications (Cochrane Database Syst Rev 2010 Jul 7) update
AHFS data updated
addition of prolonged-release ropinirole to levodopa therapy may delay onset of dyskinesia in patients with Parkinson disease (Mov Disord 2010 May 15) update
Related Summaries:
Hyperprolactinemia
Parkinson disease
Overview:
ergot-derivative dopamine receptor agonist and prolactin inhibitor
brand name Dostinex, available generically
FDA approved for treatment of hyperprolactinemia
initial dose 0.25 mg orally twice weekly
increase by 0.25 mg twice weekly up to 1 mg twice weekly, use lowest effective dose
consider decreasing dose if normal serum prolactin levels for 24 months and tumor size decreased ≥ 50%
cabergoline appears at least as effective and better tolerated than bromocriptine in women with hyperprolactinemia (level 2 [mid-level] evidence)
has been used for Parkinson disease but other dopamine agonists more commonly used
contraindicated if uncontrolled hypertension
adverse effects may include pleural effusion, pulmonary fibrosis, cardiac valvulopathy, orthostatic hypotension, nausea, constipation, abdominal pain, headache, dizziness, asthenia, fatigue
cabergoline may be associated with cardiac valve regurgitation (level 2 [mid-level] evidence)
Pregnancy Category B
available in 0.5 mg scored tablets
General Information
Description:
An ergot-derivative dopamine receptor agonist and prolactin inhibitor. 1 2 3 8 10 11 12 15
Class:
Class: Ergot-derivative Dopamine Receptor Agonists
Brand:
Dostinex®
Chemical Name:
1-[(6-allylergolin-8β-yl)-carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea
Uses and Efficacy
Uses:
Hyperprolactinemic Disorders:
Treatment of hyperprolactinemic disorders due to prolactinoma (prolactin-secreting adenomas) or idiopathic hyperprolactinemia. 1 2 3 12 13 14 Suppresses prolactin secretion, restores gonadal function, and reduces the size of prolactinomas. 1 2 3 12 13 14
At least as effective as bromocriptine in normalizing serum prolactin concentrations and restoring gonadal function in women with hyperprolactinemic amenorrhea. 12 13 Fewer adverse effects, especially adverse GI effects, reported in cabergoline-treated women than in bromocriptine-treated women. 12 13 14 Bromocriptine preferred when restoration of fertility is the goal of therapy; this recommendation is based on the safety record of bromocriptine in pregnant women. 14
Parkinsonian Syndrome:
Has been used for the symptomatic management of parkinsonian syndrome †. 4 5 6 7 8 9 10 11
Has been used as monotherapy for initial symptomatic management of parkinsonian syndrome †. 8 9 11 Most clinicians would use levodopa for initial therapy in individuals >70 years of age (less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction), in patients with cognitive impairment, and in those with severe disease. 7 A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age. 7
Has been used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome † in patients with advanced disease. 4 5 6 8 10
Efficacy:
Hyperprolactinemia:
cabergoline appears at least as effective and better tolerated than bromocriptine in women with hyperprolactinemia (level 2 [mid-level] evidence)
based on randomized trial with partial blinding
459 amenorrheic women with pituitary microadenomas or idiopathic hyperprolactinemia were randomized to cabergoline 0.5-1 mg twice weekly vs. bromocriptine 2.5-5 mg twice daily
treatment was double-blind for 8 weeks then open-label to allow unbiased assessment of side effects initially
comparing cabergoline vs. bromocriptine
stable normoprolactinemia in 83% vs. 59% (p < 0.001, NNT 5)
ovulatory cycles or pregnancy occurred in 72% vs. 52% (p < 0.001, NNT 5)
amenorrhea persisted in 7% vs. 16%
adverse effects in 68% vs. 78% (p = 0.03, NNT 10), or 63% vs. 71% during double-blind period (p = 0.07)
drug discontinuation due to adverse effects in 3% vs. 12% (p < 0.001, NNT 12)
nausea in 31% vs. 50% (p < 0.001, NNT 6)
Reference - N Engl J Med 1994 Oct 6;331(14):904
Parkinson disease:
cabergoline can reduce levodopa dose and may modestly improve motor impairment and disability
based on Cochrane review
systematic review of 3 trials with 268 patients with Parkinson disease and motor complications
reduction of 1.14 hours (95% CI -0.06 to 2.33, p = 0.06) in off time in favor of cabergoline was not statistically significant
inadequate data on dyskinesia
levodopa dose reduction was significantly greater with cabergoline
nonsignificant trend towards more dopaminergic adverse events with cabergoline
nonsignificant trend towards fewer withdrawals from cabergoline
Reference - systematic review last updated 2000 Nov 17 (Cochrane Library 2001 Issue 1:CD001518)
cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment, disability ratings, and levodopa dose reduction over the first 3 months of therapy
based on Cochrane review
systematic review of 5 trials with 1,071 patients
adverse event profile and withdrawals similar except dyskinesia and confusion were increased with cabergoline
Reference - systematic review last updated 2000 Nov 17 (Cochrane Library 2001 Issue 1:CD001519)
dopamine agonists for Parkinson disease (drug class considerations)
dopamine agonist may reduce risk of motor complications but associated with more adverse events than levodopa in patients with early Parkinson disease (level 2 [mid-level] evidence)
based on Cochrane review of trials with methodologic limitations
systematic review of 29 randomized trials evaluating oral dopamine agonist therapy in 5,247 patients with early Parkinson disease
methodologic limitations included inadequate or unclear description of randomization (16 trials) and allocation concealment (23 trials), unclear use of intention-to-treat analysis
compared to levodopa alone, dopamine agonist (with or without levodopa) associated with reduced incidence of
dyskinesia in 18 trials with 3,404 patients (p < 0.00001), results limited by heterogeneity (p = 0.006)
dystonia in 11 trials with 1,896 patients (p = 0.0002)
motor fluctuations in 12 trials with 2,580 patients (p = 0.002)
comparing dopamine agonists (with or without levodopa) to control (placebo or levodopa) on adverse effects
dopamine agonists associated with increased
edema in analysis of 6 trials with 1,650 patients
odds ratio 3.48 (95% CI 2.53-4.79)
NNH 6-14 assuming 5% edema in controls
somnolence in analysis of 11 trials with 2,423 patients
odds ratio 2.18 (95% CI 1.75-2.72)
NNH 7-14 assuming 11% somnolence in controls
constipation in analysis of 8 trials with 1,961 patients
odds ratio 1.8 (95% CI 1.36-2.39)
NNH 9-35 assuming 9% constipation in controls
dizziness in analysis of 13 trials with 2,294 patients
odds ratio 1.6 (95% CI 1.28-2.01)
NNH 8-29 assuming 15% dizziness in controls
hallucinations in analysis of 14 trials with 2,479 patients
odds ratio 2.22 (95% CI 1.58-3.12)
NNH 13-45 assuming 4% hallucinations in controls
nausea in 34.4% vs. 23.1% in analysis of 15 trials with 2,631 patients
odds ratio 1.86 (95% CI 1.56-2.23)
NNH 5-11 assuming 23% nausea in controls
discontinuation of treatment due to adverse events in 16.3% vs. 7% in analysis of 25 trials with 4,719 patients
odds ratio 2.49 (95% CI 2.08-2.98)
NNH 8-15 assuming 7% discontinuation of treatment in controls
symptomatic control of Parkinson disease better with levodopa than dopamine agonists, but data too inconsistent and incomplete for meta-analysis
Reference - Cochrane Database Syst Rev 2008 Apr 16;(2):CD006564, Cochrane for Clinicians summary can be found in Am Fam Physician 2009 Jul 1;80(1):28
addition of dopamine agonists to levodopa therapy may improve activities of daily function but increase rates of dyskinesia and hallucinations in patients with Parkinson disease (level 2 [mid-level] evidence)
based on systematic review without assessment of allocation concealment
systematic review of 15 randomized placebo-controlled trials of dopamine agonist in 4,380 patients with Parkinson disease on levodopa therapy
non-ergot dopamine agonists (pramipexole, ropinirole, sumanirole, piribedil and rotigotine) and ergot dopamine agonists (pergolide, cabergoline and bromocriptine) were evaluated; treatments lasted 12-40 weeks
trial quality assessment did not evaluate allocation concealment or intention-to-treat analysis
use of adjunct dopamine agonist associated with
improved activities of daily living scores (p < 0.0001) in analysis of 10 trials with 2,335 patients
improved motor scores (p < 0.0001) in analysis of 9 trials with 2,226 patients, analysis limited by statistical heterogeneity
reduction in "off" time (p < 0.0001) in analysis of 4 trials with 1,851 patients, analysis limited by statistical heterogeneity
reduction in levodopa dose (p < 0.0001) in analysis of 5 trials with 1,233 patients
increased rate of dyskinesias in analysis of 12 trials with 4,076 patients
odds ratio 3.34 (95% CI 2.71-4.11)
NNH 4-6 assuming 12% dyskinesias in controls
increased rate of hallucinations in analysis of 13 trials with 4,082 patients
odds ratio 3.58 (95% CI 2.64-4.86)
NNH 9-21 assuming 3% hallucinations in controls
no significant difference between dopamine agonist and placebo groups in number of patient withdrawals
Reference - Int J Clin Pract 2009 Apr;63(4):613
adjuvant therapy in later disease may reduce off-time and levodopa use and improve Unified Parkinson's Disease Rating Scale scores in patients with motor complications (level 2 [mid-level] evidence)
based on Cochrane review with inadequate assessment of trial quality
systematic review of 44 randomized placebo-controlled trials evaluating oral dopamine agonists, COMT inhibitors, or MAO-B inhibitors as adjuvant therapy to levodopa in 8,436 patients with later stage Parkinson disease experiencing motor complication
quality assessment included only randomization sequence generation (adequate in 26 trials), allocation concealment (adequate in 5 trials), and blinding (adequate in all trials)
indirect comparisons suggest dopamine agonists more effective than COMT inhibitors and MAO-B inhibitors
Reference - Cochrane Database Syst Rev 2010 Jul 7;(7):CD007166
Restless legs syndrome:
cabergoline is effective for restless leg syndrome (level 1 [likely reliable] evidence)
based on randomized trial
40 patients ages 18-75 years with restless leg syndrome were randomized to cabergoline vs. placebo at bedtime for 5 weeks
cabergoline 0.5 mg dose was increased in 0.5 mg increments over 14 days to final dose of 2 mg
domperidone could be prescribed for any patients complaining of gastrointestinal side effects
comparing cabergoline vs. placebo
mean periodic leg movements during sleep arousal index < 5/hour vs. 20/hour (p = 0.0014)
mean improvement of 23.7 vs. 11.4 on 60-point scale measuring quality of life (p < 0.05)
80% vs. 30% were very much or much improved on Clinical Global Impressions Scale (p < 0.01, NNT 2)
65% vs. 30% adverse effects (NNH 3)
22% vs. 5% nausea (NNH 5)
9% vs. 0 constipation (NNH 11)
13% vs. 0 discontinuation due to adverse effects (NNH 7)
Reference - Neurology 2006 Sep 26;67(6):1040
Dosage and Administration
Administration:
Oral Administration:
Administer orally without regard to meals. 1
Hyperprolactinemic disorders: Administer twice weekly. 1
Parkinsonian syndrome: Administer once daily. 8
Dosage:
Adults:
Hyperprolactinemic Disorders:
Oral:
Initiate at low dosage and increase slowly (at ≥4 week intervals) until therapeutic response is achieved. 1
Initially, 0.25 mg twice weekly; increase in increments of 0.25 mg twice weekly up to 1 mg twice weekly. 1 Base dosage adjustments on serum prolactin concentrations; use lowest effective dosage. 1
Consider decreasing the dosage if normal serum prolactin concentrations maintained for 24 months and size of tumor decreased ≥50%; periodically monitor to determine whether retreatment is needed. 14 15 Some patients (e.g., those with microadenomas) may be able to discontinue the drug; discontinuance in those with macroadenomas should be undertaken with extreme caution. 14 15 The manufacturer states that efficacy >24 months not established. 1
Parkinsonian Syndrome †:
Oral:
Initiate at low dosage and increase slowly (at intervals of 7 or 14 days) until the maximum therapeutic response is achieved. 8
2–6 mg daily has been used. 8
Therapy has been initiated with 1 mg once daily, then increased in increments of 0.5–1 mg at 7 or 14 day intervals until control of symptoms obtained. 8
When cabergoline is used as an adjunct to levodopa, the levodopa dosage may be decreased gradually as tolerated. 8
When therapy with a dopamine receptor agonist is discontinued, the drug is discontinued gradually. 18
Prescribing Limits:
Adults:
Hyperprolactinemic Disorders:
Oral:
Dosages >1 mg twice weekly have not been systematically evaluated. 1
Special Populations:
Hepatic Impairment:
No specific dosage recommendations at this time; use with caution in patients with severe hepatic impairment. 1 (See Hepatic Impairment under Cautions and also see Absorption: Special Populations, under Pharmacokinetics.)
Renal Impairment:
No specific dosage recommendations at this time. 1(See Elimination: Special Populations, under Pharmacokinetics.)
Geriatric Patients:
Select dosage carefully; start at low dosage. 1(See Geriatric Use under Cautions.)
Cautions and Adverse Effects
Contraindications:
Known hypersensitivity to cabergoline or other ergot derivatives. 1
Uncontrolled hypertension. 1
Warnings/Precautions:
Warnings:
Hypertension during Pregnancy:
Should not be used in patients with pregnancy-induced hypertension (e.g., preeclampsia, eclampsia) unless potential benefits outweigh possible risks. 1
Fibrotic Effects:
Pleural effusion, pulmonary fibrosis, and cardiac valvulopathy reported. 1 16Signs and symptoms have improved after discontinuance. 1
Use with caution in patients with history of, or current signs and/or symptoms of, respiratory or cardiac disorders linked to fibrotic tissue. 1
General Precautions:
When used for parkinsonian syndrome, observe the usual precautions associated with dopamine receptor agonist therapy in this patient population. 8 9 17 18 Usual dosage for parkinsonian syndrome exceeds dosage used for hyperprolactinemia. 1 17
Symptomatic Hypotension:
Orthostatic hypotension reported, especially if initial doses >1 mg are used. 1 Exercise care in patients currently receiving drugs known to lower BP. 1
Postpartum Breast Engorgement:
Not indicated for the inhibition or suppression of lactation. 1 Hypertension, cerebrovascular accidents, and seizures reported rarely when another dopamine receptor agonist (i.e., bromocriptine) was used for this indication. 1
Specific Populations:
Pregnancy:
Category B. 1 (See Hypertension during Pregnancy under Cautions.)
Lactation:
Not known whether cabergoline is distributed into milk; drug is expected to interfere with lactation. 1 Discontinue nursing or the drug. 1
Pediatric Use:
Safety and efficacy not established. 1
Geriatric Use:
Insufficient experience from clinical studies to determine whether patients ≥65 years of age respond differently than younger adults. 1 Other clinical experience has not identified age-related differences in responses. 1
Select dosage carefully, generally initiating therapy at low dosage. 1 Consider the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or drug therapy in geriatric patients. 1 2 3
Hepatic Impairment:
Cabergoline extensively metabolized in liver; use with caution and monitor carefully. 1(See Absorption: Special Populations, under Pharmacokinetics.)
Common Adverse Effects:
Patients with hyperprolactinemia: Nausea, constipation, abdominal pain, headache, dizziness, asthenia, fatigue, somnolence. 1
Patients with parkinsonian syndrome †: Dyskinesia, hallucinations, confusion, peripheral edema. 1
Heart valvulopathy with dopamine agonists:
some dopamine agonists (pergolide or cabergoline) may be associated with cardiac valve regurgitation (level 2 [mid-level] evidence)
based on case-control study, and cohort studies with asymptomatic cases
nested case-control study
conducted within cohort of 11,417 patients ages 40-80 years in United Kingdom General Practice Research Database who were prescribed antiparkinsonian drugs (levodopa, selegiline, bromocriptine, cabergoline, pergolide, lisuride, pramipexole, ropinirole) 1988-2005
31 cases had newly diagnosed mitral regurgitation (26 cases), aortic regurgitation (12 cases) or tricuspid regurgitation (3 cases); 8 cases had multiple valves involved
663 controls matched on age, sex and year of entry
drugs associated with cardiac valve regurgitation were
pergolide (incidence rate ratio 7.1, 95% CI 2.3-22.3) based on 6 cases (19% cases vs. 4% controls)
cabergoline (incidence rate ratio 4.9, 95% CI 1.5-15.6) based on 6 cases (19% cases vs. 5% controls)
no cases had exposure to bromocriptine, lisuride, pramipexole or ropinirole and few (0 to 3%) controls had exposure to these drugs
Reference - N Engl J Med 2007 Jan 4;356(1):29, editorial can be found in N Engl J Med 2007 Jan 4;356(1):6, commentary can be found in N Engl J Med 2007 Apr 19;356(16):1676, ACP J Club 2007 May-Jun;146(3):75 EBSCOhost Full Text
pergolide use in Parkinson disease associated with heart valve disease (level 3 [lacking direct] evidence)
based on meta-analysis of 7 studies with 394 patients treated with pergolide mesylate and 280 controls (without clinical outcomes)
pergolide associated with moderate to severe regurgitation (odds ratio 3.1, 95% CI 1.7-5.6)
Reference - Arch Neurol 2007 Dec;64(12):1721
cohort studies using echocardiography
cabergoline and pergolide associated with moderate-to-severe cardiac valve regurgitation
echocardiography performed in
64 patients with Parkinson's disease taking pergolide for at least 12 months
49 patients with Parkinson's disease taking cabergoline for at least 12 months
42 patients with Parkinson's disease taking non-ergot-derived dopamine agonist (pramipexole or ropinirole) for at least 12 months
90 controls recruited from relatives of patients or acquaintances of medical staff
moderate-to-severe mitral regurgitation found in 9 (14%) pergolide group, 5 (10%) cabergoline group, 0 non-ergot-derived dopamine agonist group and 2 (2%) controls
moderate-to-severe aortic regurgitation found in 9 (14%) pergolide group, 12 (24%) cabergoline group, 0 non-ergot-derived dopamine agonist group and 3 (3%) controls
moderate-to-severe tricuspid regurgitation found in 4 (6%) pergolide group, 3 (6%) cabergoline group, 0 non-ergot-derived dopamine agonist group and 1 (1%) control
rate of any moderate-to-severe cardiac valve regurgitation
0 for patients exposed to non-ergot-derived dopamine agonists
6% for controls
23% for pergolide (NNH 5)
29% for cabergoline (NNH 4)
Reference - N Engl J Med 2007 Jan 4;356(1):39, editorial can be found in N Engl J Med 2007 Jan 4;356(1):6, commentary can be found in ACP J Club 2007 May-Jun;146(3):75 EBSCOhost Full Text
pergolide associated with restrictive valvular heart disease on echocardiography
78 Parkinson disease patients using pergolide and 18 Parkinson disease patients not taking pergolide underwent echocardiography
comparing pergolide users vs. controls
33% vs. 0 had restrictive valvular heart disease of any type
19% vs. 0 had "important" disease
Reference - Lancet 2004 Apr 10;363(9416):1179 EBSCOhost Full Text, commentary can be found in Lancet 2004 Jun 5;363(9424):1907 EBSCOhost Full Text, Am Fam Physician 2005 Feb 1;71(3):584
pergolide use may be associated with aortic regurgitation but not severe regurgitation
retrospective study of 118 patients who had "pergolide" or "Permax" in the typed medical record notes and had echocardiography
comparing 55 patients who had echocardiography at least 6 months after starting pergolide vs. 63 patients who had echocardiography before starting pergolide or within 1 month of starting pergolide
25 of 55 (45%) vs. 13 of 63 (21%) had aortic valve regurgitation (p = 0.006, NNH 4)
no significant differences in rates of tricuspid valve regurgitation (78% vs. 76%), mitral valve regurgitation (71% vs. 65%), any valve regurgitation (85% vs. 79%), severe tricuspid regurgitation (11% vs. 8%), severe mitral regurgitation (13% vs. 5%), severe aortic regurgitation (13% vs. 8%) or any severe regurgitation (24% vs. 14%)
Reference - Mayo Clin Proc 2005 Aug;80(8):1016 EBSCOhost Full Text
pergolide (Permax) associated with valvular heart disease in 15 reports collected by FDA (Mayo Clin Proc 2003 Jun;78(6):730 EBSCOhost Full Text PDF), editorial can be found in Mayo Clin Proc 2003 Jun;78(6):684 EBSCOhost Full Text PDF
case report of cabergoline-related severe restrictive mitral regurgitation can be found in N Engl J Med 2005 Nov 3;353(18):1976, commentary can be found in N Engl J Med 2006 Jan 26;354(4):420
Additional Adverse Effect Information:
dopamine agonists may increase risk of sudden uncontrollable somnolence (level 2 [mid-level] evidence)
based on observational studies
interview and medical record review of 929 Parkinson disease patients
22% reported sudden uncontrollable somnolence in preceding 6 months
episodes reported by 13% those taking levodopa-carbidopa monotherapy, 22% taking dopamine agonist monotherapy, and 28% taking both
Reference - Arch Neurol 2005 Aug;62(8):1242 in J Watch Online 2005 Aug 30
excessive daytime sleepiness reported in 51% of cohort of 638 highly functional Parkinson disease patients
16 patients (3.8%) had sudden onset of sleep while driving
daytime sleepiness and sleep attacks while driving were NOT associated with any antiparkinson drugs or drug classes
Reference - JAMA 2002 Jan 23-30;287(4):455, editorial can be found in JAMA 2002 Jan 23-30;287(4):509, commentary can be found in JAMA 2002 Apr 24;287(16):2076
review of sleep attacks with dopamine agonists identified 124 patients in 20 publications but found insufficient data to provide specific recommendations (BMJ 2002 Jun 22;324(7352):1483 full-text), commentary can be found in BMJ 2002 Sep 21;325(7365):657 full-text
initiation of dopamine agonist therapy may be associated with acute orthostatic hypotension (level 2 [mid-level] evidence)
based on study of 29 patients with Parkinson disease given pergolide, pramipexole or ropinirole then blood pressure measured supine and standing on 3 occasions
10 (34%) had orthostatic hypotension defined as drop in systolic blood pressure > 25 mm Hg or diastolic blood pressure > 10 mm Hg
only 3 (10%) had symptoms of orthostatic hypotension such as lightheadedness or malaise
Reference - Arch Neurol 2000 Oct;57(10):1461
pathological gambling reported in 11 patients within 30 months of starting dopamine agonist for Parkinson disease (level 3 [lacking direct] evidence)
effect within 3 months in 7 of these patients
17 other cases reported in the literature
19 of these 28 cases (68%) associated with pramipexole
Reference - Arch Neurol 2005 Sep;62(9):1377
new onset gambling or hypersexuality seen in 7 of 38 patients taking therapeutic doses of dopamine agonists or levodopa-carbidopa in retrospective study (Mayo Clin Proc 2009 Apr;84(4):310 EBSCOhost Full Text)
Interactions
Specific Drugs:
Drug Interaction Comments
Dopamine antagonists (e.g., phenothiazines, butyrophenones, thioxanthenes, metoclopramide) Possible reduced efficacy of cabergoline 1 Generally should not be used concomitantly 1 8
Levodopa Additive therapeutic and/or adverse (e.g., dyskinesia) effects 8 Consider a reduction in levodopa dosage when cabergoline is added to levodopa therapy 8
Mechanism of Action/Pharmacokinetics
Actions:
A long-acting dopamine receptor agonist; has high binding affinity for dopamine D2 receptors and lesser affinity for D1, α1- and α2-adrenergic, and serotonin (5-HT1 and 5-HT2) receptors. 1 8
Reduces serum prolactin concentrations by inhibiting release of prolactin from the anterior pituitary gland. 1 This effect on hypothalamic/pituitary function attributed to the drug's agonist activity at D2 receptors. 1
Pharmacokinetics:
Absorption:
Bioavailability:
Peak plasma concentrations usually attained within 1–2 hours. 1 17
Absolute bioavailability unknown. 1 17
Onset:
Following oral administration of a single 0.6-mg dose of cabergoline, time to maximum prolactin-lowering effect was 48 hours. 1
Duration:
Prolactin-lowering effect persists for 14 days. 1
Food:
Food does not alter the pharmacokinetics of cabergoline. 1
Special Populations:
Peak plasma concentrations and AUC not altered in patients with mild to moderate hepatic impairment (Child Pugh score ≤10). 1 Peak plasma concentrations and AUC substantially increased in patients with severe impairment (Child Pugh score >10). 1
Distribution:
Extent:
Extensively distributed throughout the body, including the CNS. 1 8
Plasma Protein Binding:
40–42%. 1 17
Elimination:
Metabolism:
Metabolized in the liver (minimal CYP involvement), mainly by hydrolysis of the acylurea bond; 1 17 undergoes substantial first-pass metabolism. 1
Elimination Route:
Excreted in feces (72%) and in urine (18% as metabolites and unchanged drug). 17
Half-life:
63–109 hours. 1 17
Special Populations:
Pharmacokinetic values not altered in patients with moderate to severe renal impairment. 1 17
Stability and Compatibility
Storage:
Oral:
Tablets:
20–25°C. 1
Preparations
Tables of Preparations:
Cabergoline Routes Dosage Forms Strengths Brand Names Manufacturer
Oral Tablets 0.5 mg Dostinex® (scored) Pfizer
Cabergoline Teva, Par
Medication Cost Assistance Programs:
medication cost assistance programs for Cabergoline from NeedyMeds
Patient Information
Advice to Patients:
Potential for hypotension. 1
Importance of patients informing clinicians if cough or dyspnea develop. 1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., respiratory or cardiac disorders associated with fibrosis). 1
Importance of informing patients of other important precautionary information. 1 (See Cautions.)
References
